A two-stage process of cancer induction has been reported in several diverse biological systems, and suggested to be a general feature of the mechanism of carcinogenesis by chemicals. Most experiments have used different agents to induce the initiation and promotion phases and the question of the identity of the promoting stimulus in cancer by a single chemical agent has received little attention. Common to both promotion by phorbol esters alone and complete carcinogenesis by polycyclic aromatic hydrocarbons is that, in order to elicit tumors, both require the frequent application of promoter or carcinogen respectively. This finding infers that, especially in the case of this type of agent, a two-stage mechanism is operative. The similarities in response to tumor-promoting agents of mouse skin tumorigenesis and Chinese hamster V79 cell mutagenesis systems suggest that the latter may be suitable for addressing the above question. V79 cells do not have metabolic enzymes required for conversion of precarcinogens to initiators, but this activity can be supplied exogenously as required; therefore clear separation of initiating and promoting activity of precarcinogens or their metabolites is possible using this cell type. The study will consist of three phases: a) Determination of mutation frequencies in V79 cells induced by reactive mutagenic metabolites of carcinogenic agents. b) Determination of mutation frenquencies in V79 cells treated with precarcinogens and weakly or non-mutagenic metabolites of precarcinogens. c) Study of the effect of aromatic precarcinogens and weakly or non-mutagenic carcinogen metabolites on mutagenic metabolite-induced mutation frequences in V79 cells.